The candidate, Beatrice E. Gee, M.D., is a pediatric hematologist trained at Children's Hospital, Boston and Dana Farber Cancer Institute. She has past experience studying red cell membrane adhesion molecules. This proposed project will extend her research expertise to include molecular biology and transgenic mouse methodologies to the study of sickle cell vasculopathy. Student Candidate: Leslie O. Ibeanusi is a sophomore student at Spelman College who aspires to become a pediatric clinician-scientist. She has past experience studying sickle cell disease and is interested in vascular biology and molecular techniques. The Proposal: Under the mentorship of Gary H. Gibbons, M.D., Bruce A. Freeman, Ph.D., and Tim Townes, Ph.D., she proposes to study in vitro and in vivo aspects of erythrocyte-endothelial cell interactions, with specific attention to the roles of the alpha4betal integrin-VCAM-1 interactions and production of reactive oxygen species on red cell adhesion, endothelial cell gene expression, and vascular remodelling. The specific objectives of the proposal include: 1. To examine the effects of xanthine oxidase, hydrogen peroxide, and allopurinol on in vitro sickle erythrocyte interactions with human brain microvascular cells (HBEC), and to characterize gene expression profiles of HBEC under the various conditions; 2. To characterize erythrocyte-endothelial cell interactions and the mediator role of oxidative stress in transgenic mice; 3a. To develop a transgenic mouse expressing human sickle hemoglobin that is also deficient in reticulocyte alpha4 integrin; and 3b. To characterize the vascular phenotype of this multiply mutated mouse The Environment: Morehouse School of Medicine is a Historically Black University with a very active and growing basic science research community. Dr. Gibbons, the primary mentor, has a very active cardiovascular research program and extensive experience mentoring clinician-scientists. Co-mentors, Drs. Freeman and Townes at Univ. of Alabama, Birmingham, are also experts in their fields.